Zytiga250 mg

Zytiga is a CYP17 (androgen biosynthesis) inhibitor used, in combination with corticosteroid therapy, for the treatment of prostate cancer in adult men. It is always used together with ongoing medical or surgical castration (androgen deprivation therapy).

FDA-approved / Established Indications

• Metastatic castration-resistant prostate cancer (mCRPC): Zytiga in combination with prednisone (or prednisolone) is indicated for men with mCRPC, including those previously treated with chemotherapy and those who are chemotherapy-naive.
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC): Zytiga in combination with prednisone is indicated for men with newly diagnosed, high-risk metastatic castration-sensitive prostate cancer, given together with a GnRH analog (or after bilateral orchiectomy).

Zytiga is not indicated for use in women and has no role in the treatment of any condition outside prostate cancer.

Each film-coated tablet contains Abiraterone Acetate as the active ingredient, commonly available in strengths of 250 mg and 500 mg. Formulations may differ slightly in bioavailability between manufacturers, so tablets from different brands or strengths should not be substituted interchangeably without medical advice.

Zytiga is an oral antiandrogen and androgen biosynthesis inhibitor used in the management of advanced prostate cancer. It is a prodrug that is converted in the body to abiraterone, which selectively and irreversibly inhibits the CYP17 (17α-hydroxylase/C17,20-lyase) enzyme, a key enzyme required for androgen (testosterone) production in the testes, adrenal glands, and prostate tumor tissue itself.

By blocking this enzyme, Zytiga reduces circulating androgen levels below what surgical or medical castration alone can achieve, which can slow the growth of androgen-dependent prostate cancer. Because inhibiting CYP17 also increases upstream mineralocorticoid precursors, Zytiga is always co-administered with a corticosteroid (prednisone/prednisolone) to reduce mineralocorticoid-related side effects such as high blood pressure, low potassium, and fluid retention.

Zytiga belongs to the therapeutic class of antiandrogens / androgen biosynthesis inhibitors (CYP17 inhibitors), a subclass of antineoplastic (anticancer) hormonal agents used specifically in prostate cancer.

Abiraterone Acetate is hydrolyzed in vivo to abiraterone, the active moiety. Abiraterone is a selective, irreversible inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase), an enzyme expressed in testicular, adrenal, and prostatic tumor tissues that is required for two sequential steps of androgen biosynthesis.

By inhibiting CYP17, Abiraterone Acetate suppresses production of testosterone and other androgens from all three sources, achieving androgen suppression beyond that produced by gonadotropin-releasing hormone (GnRH) analogs or orchiectomy alone. This is the basis for its efficacy in castration-resistant and high-risk castration-sensitive prostate cancer.

A pharmacologic consequence of CYP17 inhibition is a compensatory rise in adrenocorticotropic hormone (ACTH), leading to increased mineralocorticoid production (deoxycorticosterone), which underlies the characteristic side effects of hypertension, hypokalemia, and fluid retention; co-administered corticosteroid suppresses ACTH and mitigates this effect.

Absorption of Abiraterone Acetate is markedly increased by food (several-fold), which is why it must be taken on an empty stomach; abiraterone is metabolized mainly by hepatic enzymes including SULT2A1 and CYP3A4, and it is itself a moderate inhibitor of CYP2D6 and CYP2C8 hepatic enzymes.

Take Zytiga orally on a completely empty stomach — at least 1 hour before or 2 hours after any food — swallowing the tablet(s) whole with water. Do not crush, break, or chew the tablets. Take at approximately the same time each day, together with the prescribed corticosteroid dose.

The following interactions with Zytiga are clinically significant and well documented:

• Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort): these can substantially reduce abiraterone plasma concentrations (rifampin reduced exposure by roughly half), potentially reducing efficacy. Combination should be avoided; if unavoidable, the dosing frequency of Zytiga may need to be increased under medical supervision.
• CYP2D6 substrates with a narrow therapeutic index (e.g., certain antiarrhythmics, tricyclic antidepressants): Zytiga inhibits CYP2D6 and can raise plasma levels of these drugs; avoid co-administration where possible or use with caution and dose adjustment.
• CYP2C8 substrates (e.g., pioglitazone, paclitaxel, repaglinide): Zytiga inhibits CYP2C8 and increased pioglitazone exposure by about 46% in studies; monitor for toxicity of the co-administered drug.
• Spironolactone: has mineralocorticoid receptor–agonist activity and can worsen or mask the mineralocorticoid-excess effects of Zytiga; concurrent use should generally be avoided.
• Drugs affecting gastric pH or food: taking Zytiga with food (rather than on an empty stomach) markedly increases absorption and should be avoided, as described in Dosage and Administration.

Inform the prescribing physician of all other medicines, herbal products, and supplements being used before starting Zytiga.

Common side effects of Zytiga (occurring in more than 10% of patients) include:

• Fatigue
• Joint swelling or discomfort (arthralgia)
• Edema (fluid retention/swelling of the legs)
• Hot flushes
• Hypertension (high blood pressure)
• Diarrhea and nausea/vomiting
• Urinary tract infection
• Cough and upper respiratory infection
• Headache

Serious Side Effects

• Mineralocorticoid excess: hypertension, hypokalemia (low potassium), and fluid retention, related to the drug's mechanism of action.
• Adrenocortical insufficiency: especially during illness, physical stress, or abrupt discontinuation of the co-administered corticosteroid; symptoms include weakness, dizziness, and low blood pressure.
• Hepatotoxicity: elevations in liver enzymes and bilirubin; rare cases of severe liver injury have been reported.
• Laboratory abnormalities: anemia, elevated alkaline phosphatase, high triglycerides, low lymphocyte count, and high blood sugar.

Patients should promptly report symptoms of these serious effects to their physician; see Precautions and Warnings for monitoring guidance.

Zytiga is not indicated for use in women and must not be used by women who are pregnant or who may become pregnant, as it can cause fetal harm based on its mechanism of action. Women who are pregnant or planning to become pregnant should not handle Zytiga tablets, especially broken or crushed tablets, without protective gloves.

Male patients with female partners of reproductive potential should use effective contraception during treatment with Zytiga and for a period after the last dose, as advised by their physician, because trace amounts of the drug may be present in semen.

There is no relevant data on use of Zytiga during breastfeeding, as the drug is not intended for use in women. Consult a physician for any exposure-related concerns.

Empty-Stomach Dosing Requirement

Zytiga must be taken strictly on an empty stomach. Taking it with food significantly increases drug absorption and can lead to exposure levels associated with an increased risk of toxicity. See Dosage and Administration.

Mineralocorticoid Excess

Zytiga can cause hypertension, hypokalemia, and fluid retention due to increased mineralocorticoid production. Blood pressure, serum potassium, and signs of fluid retention should be monitored monthly throughout treatment, and pre-existing heart failure, hypertension, or hypokalemia should be controlled before starting therapy.

Adrenocortical Insufficiency

Because Zytiga suppresses androgen and cortisol-pathway synthesis, adrenocortical insufficiency can occur, particularly during periods of stress, illness, surgery, or if the co-administered corticosteroid is stopped or reduced abruptly. The corticosteroid dose should never be stopped or changed without medical guidance, and increased corticosteroid coverage may be needed before, during, and after stressful situations.

Hepatotoxicity

Liver function tests (ALT, AST, bilirubin) must be checked before starting Zytiga, every two weeks for the first three months, and monthly thereafter. Treatment may need to be interrupted, dose-reduced, or permanently discontinued if significant liver enzyme elevations occur.

Not for Use in Women

Zytiga is intended only for use in male patients with prostate cancer and must never be given to women (see Contraindications and Pregnancy and Lactation).

Cardiovascular Monitoring

Because of its effects on blood pressure, fluid balance, and potassium, cardiovascular status should be monitored throughout treatment, especially in patients with pre-existing cardiac disease.

There is no specific antidote for Zytiga overdose. In case of a suspected overdose, seek immediate medical attention or contact emergency services / a poison control center right away.

In a hospital setting, management is supportive and includes close monitoring of cardiac function (including heart rhythm), blood pressure, serum potassium, and liver function, with treatment directed at any specific symptoms that develop. Patients or caregivers should not attempt to manage a suspected overdose at home.

Store at 20°C to 25°C (68°F to 77°F); brief excursions between 15°C and 30°C are permitted. Keep the container tightly closed, protected from light and moisture, and out of the reach of children and pregnant women.

Use in Women

Zytiga is not indicated for use in women under any circumstance (see Contraindications).

Pediatric Use

Zytiga is indicated only for adult men with prostate cancer. Safety and effectiveness in children have not been established, and there is no pediatric indication for this drug.

Elderly Patients

No overall differences in safety or effectiveness have been observed between elderly and younger patients in clinical trials; since Zytiga is used in a population that is predominantly older men, standard dosing generally applies, with the same monitoring precautions as for all patients.

Hepatic Impairment

• Mild impairment (Child-Pugh Class A): no dose adjustment needed.
• Moderate impairment (Child-Pugh Class B): reduce dose to 250 mg once daily.
• Severe impairment (Child-Pugh Class C): Zytiga is contraindicated (see Contraindications).

Renal Impairment

No dose adjustment of Zytiga is required in patients with renal impairment; however, caution and monitoring are advised in patients with severe renal disease.

Treatment with Zytiga is continued for as long as it provides clinical benefit — typically until there is evidence of disease progression or unacceptable toxicity develops — as determined and monitored by the treating oncologist/urologist. It should not be stopped or its dose changed without medical advice, given the need to also manage the co-administered corticosteroid safely.

Abiraterone Acetate is classified as an antiandrogen and CYP17 (androgen biosynthesis) inhibitor within the broader class of antineoplastic hormonal agents used in prostate cancer.

Abiraterone Acetate is converted in the body to abiraterone, which irreversibly inhibits CYP17 (17α-hydroxylase/C17,20-lyase), a key enzyme in androgen synthesis present in testicular, adrenal, and prostate tumor tissue. This blocks production of testosterone and other androgens from all sources, depriving androgen-dependent prostate cancer cells of the hormonal stimulation they need to grow, beyond what medical or surgical castration alone achieves.

Zytiga has no approved pediatric indication. It is used exclusively in adult men with prostate cancer, and safety and effectiveness in pediatric patients have not been established; it should not be used in children.